Cynapsus Therapeutics Inc (NASDAQ:CYNA) just closed on the details of a pivotal trial in Europe with the European Medicines Agency (EMA), and expects to kick off the study before the close of this year. This is big news in itself, but as a kicker, and much nearer term, the results of the US counterpart study should hit press over the coming weeks. If we see efficacy, the company could get an NDA with the FDA before the end of 2016, and there’ll be plenty of positive sentiment feeding into its market capitalization as the European trial runs. Here’s what matters.
As mentioned, it’s a Parkinson’s disease candidate, and it’s a reformulation of an already approved drug in this indication called apomorphine.
Those familiar with the Parkinson’s space will probably be similarly familiar with apomorphine; it’s the dopamine agonist standard of care for the OFF episode side of the condition. That is, when muscle control becomes difficult.
The drug works by stimulating receptors into producing dopamine. The issues with muscle control that are associated with Parkinson’s disease come about as a result of a dopamine deficiency, and through the administration of apomorphine, it’s become a pretty well established fact that production stimulation via these sorts of agonists can counter the issue.
The currently-approved version is a self administration injectable, and patients with moderate to severe Parkinson’s can have multiple OFF episodes throughout the day. This necessitates repeat injections, which can quickly become uncomfortable as a result of site reaction, etc.
Cynapsus Therapeutics Inc (NASDAQ:CYNA)’s version of the drug is a sublingual film administration. That means the patient puts a thin film under his or her tongue, and the drug is absorbed into the blood stream. If approved, it will be a far more comfortable way to deal with OFF episodes, and should contribute to an improved rate of adherence and QOL. If approved.
So what are we looking for from the trials? Well, the primary endpoint is the mean change from pre-dose in what’s called MDS-UPDRS Part III Motor Examination (MDS-UPDRS MOTOR). Basically, patients will take the sublingual film apomorphine at home on a daily basis, but every four weeks (across a twelve-week study period) will go into the clinic for dosing and evaluation. Thirty minutes after dosing at the clinic, the physician will perform the MDS-UPDRS MOTOR, and rate the severity of the OFF episode in question. The lower the rating, the better the improvement. The score is comprised of a raft of different factors, each of which gets its own rating, but the final rating is given as a score between 0-4, with 0 being normal and 4 being severe. As such, as an indicator of efficacy in this trial, we’re looking for a reduction from pre-dose in the rating. Say, for example, a patient is a 3 rating pre-dose, and 30 minutes after dosing is a 1 rating. That would be indicative of efficacy.
There’s a secondary endpoint measuring the number of patients that switch entirely from OFF to ON within the 30 minute period post-dose, and this will serve as a kicker to the topline efficacy readout if it comes in as hoped. Safety and tolerability aren’t really under investigation here (there’s a second phase III underway and set to close out a month after this one that is measuring safety and tolerability) but the company will no doubt take it into account come topline release day. As ever, we’re looking for the least amount of AEs possible, and the lowest possible severity of these AEs. A few grade 1 AEs, for example, won’t be an issue.
So that’s the details, what about timeframes?
Well, the phase III efficacy trial is slated to close out in October, and the safety trial in November. In all likelihood we’ll get a topline efficacy readout before the close of October, and this will be the major catalyst of the upcoming releases. Safety will compliment this come end-November, and the company reckons it can get an NDA with the agency before the end of the year. It’s cutting it tight, but this submission will also serve up some bullish momentum if everything runs smoothly going forward. Of course, the European trial should be well underway by then, so interim from that will also likely feed in to sentiment.
Note: This article is written by Mark Collins and originally published at Market Exclusive.